PROJECT SUMMARY Hair cells of the inner ear are the biological sensors that detect displacements induced by air-borne or ground-borne vibrations and transduce them into electrical signals. Estimates of the passive mechanical properties of a hair bundle indicate that its thermal fluctuations in water should be almost an order of magnitude higher than the detection threshold. How the auditory system overcomes the effects of noise to achieve its extreme sensitivity remains an open problem. In 1948, Thomas Gold first proposed that the auditory system contains an internal energy-consuming amplifier to sustain detection sensitivity under these over-damped conditions. The active process in hair cells leads to a compressive nonlinearity in the evoked response. Hair bundles of in vitro preparations have been shown to exhibit limit cycle oscillations, spontaneous motion in the absence of any input. This is one of the signatures of an underlying active process, and has been shown to lead to amplification of an applied signal. Higher order nonlinearities have been demonstrated to be ubiquitous characteristics of the hair cell response. Dependent on internal parameters and the applied stimulus, the auditory system could be poised near different bifurcations and thus exhibit different phase-locking dynamics. We propose to study how hair cells of the inner ear synchronize to high frequency signals. Specifically, we will search for regions of synchronization, of various n:m ratios between the applied and response frequencies, known in dynamic systems literature as Arnold Tongues. We will use in vitro preparations that preserve live and biologically functional hair cells, but allow direct mechanical access for application and recordings of nanometer-scale signals. To access higher frequency regimes without loading the bundles, we will use magnetic nanoparticles to apply mechanical stimulation. Comparison between recordings of vestibular and auditory systems will allow us to refine the theoretical models of the nonlinear dynamics underlying their remarkable sensitivity of detection. Next, we will explore how signals detected by the hair cells are encoded by nerve fibers. Localized mechanical stimuli, spanning the physiological range of frequencies and amplitudes, will be applied to individual hair bundles. Recordings of spike trains from the innervating neurons, elicited in response to each stimulus, will allow us to analyze the coding of information in a highly reduced system. Comparative measurements will be performed on the auditory and vestibular systems, to determine the impact of frequency selectivity on the neural code.